Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2015 Oct 27:4:e11760.
doi: 10.7554/eLife.11760.

SPOP the mutation

Leah Rider  1 , Scott D Cramer  2
Affiliations
Comment

SPOP the mutation

Leah Rider et al. Elife. .

Abstract

Prostate cancers with mutations to a protein called SPOP use an error-prone method to repair broken DNA strands.

Keywords: DNA repair; SPOP; cancer genomics; cell biology; human; human biology; medicine; mouse; prostate cancer; zebrafish.

PubMed Disclaimer

Conflict of interest statement

Competing interests:The authors declare that no competing interests exist.

Figures

Figure 1.
Figure 1.. Mutant SPOP promotes genomic rearrangements within chromosomes.
(A) SPOP mutation is an early event in a subtype of prostate cancer associated with a high genomic rearrangement frequency. The MAP3K7 and CHD1 proteins are also lost when SPOP mutations occur, and are each independently associated with high rearrangement frequencies. Based on a clonality model SPOP mutation preceeds MAP3K7 loss, which preceeds CHD1 loss. The frequency of loss for MAP3K7 (≅30%) is higher than that for CHD1 (≅15%) which is higher than the frequency with which SPOP mutation occurs (≅10%). (B) SPOP is an enzyme that enables homology-directed DNA repair (HDR) of double strand breaks. The substrate protein that is specifically involved in modulating repair is unknown. Mutant SPOP fails to promote HDR, and so the less stringent and more error prone non-homologous end joining (NHEJ) pathway becomes the favored repair pathway. This results in a high degree of intrachromosomal breaks and hence more genomic rearrangements.
See this image and copyright information in PMC

Comment on

  • SPOP mutation leads to genomic instability in prostate cancer.
    Boysen G, Barbieri CE, Prandi D, Blattner M, Chae SS, Dahija A, Nataraj S, Huang D, Marotz C, Xu L, Huang J, Lecca P, Chhangawala S, Liu D, Zhou P, Sboner A, de Bono JS, Demichelis F, Houvras Y, Rubin MA. Boysen G, et al. Elife. 2015 Sep 16;4:e09207. doi: 10.7554/eLife.09207. Elife. 2015. PMID: 26374986 Free PMC article.

References

    1. An J, Ren S, Murphy SJ, Dalangood S, Chang C, Pang X, Cui Y, Wang L, Pan Y, Zhang X, Zhu Y, Wang C, Halling GC, Cheng L, Sukov WR, Karnes RJ, Vasmatzis G, Zhang Q, Zhang J, Cheville JC, Yan J, Sun Y, Huang H. Truncated ERG Oncoproteins from TMPRSS2-ERG fusions are Resistant to SPOP-Mediated Proteasome degradation. Molecular Cell. 2015;59:904–916. doi: 10.1016/j.molcel.2015.07.025. - DOI - PubMed
    1. An J, Wang C, Deng Y, Yu L, Huang H. Destruction of full-length androgen receptor by wild-type SPOP, but not prostate-cancer-associated mutants. Cell Reports. 2014;6:657–669. doi: 10.1016/j.celrep.2014.01.013. - DOI - PMC - PubMed
    1. Baca SC, Prandi D, Lawrence MS, Mosquera JM, Romanel A, Drier Y, Park K, Kitabayashi N, MacDonald TY, Ghandi M, Van Allen E, Kryukov GV, Sboner A, Theurillat JP, Soong TD, Nickerson E, Auclair D, Tewari A, Beltran H, Onofrio RC, Boysen G, Guiducci C, Barbieri CE, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Ramos AH, Winckler W, Cipicchio M, Ardlie K, Kantoff PW, Berger MF, Gabriel SB, Golub TR, Meyerson M, Lander ES, Elemento O, Getz G, Demichelis F, Rubin MA, Garraway LA. Punctuated evolution of prostate cancer genomes. Cell. 2013;153:666–677. doi: 10.1016/j.cell.2013.03.021. - DOI - PMC - PubMed
    1. Barbieri CE, Baca SC, Lawrence MS, Demichelis F, Blattner M, Theurillat JP, White TA, Stojanov P, Van Allen E, Stransky N, Nickerson E, Chae SS, Boysen G, Auclair D, Onofrio RC, Park K, Kitabayashi N, MacDonald TY, Sheikh K, Vuong T, Guiducci C, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Hussain WM, Ramos AH, Winckler W, Redman MC, Ardlie K, Tewari AK, Mosquera JM, Rupp N, Wild PJ, Moch H, Morrissey C, Nelson PS, Kantoff PW, Gabriel SB, Golub TR, Meyerson M, Lander ES, Getz G, Rubin MA, Garraway LA. Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nature Genetics. 2012;44:685–689. doi: 10.1038/ng.2279. - DOI - PMC - PubMed
    1. Berger MF, Lawrence MS, Demichelis F, Drier Y, Cibulskis K, Sivachenko AY, Sboner A, Esgueva R, Pflueger D, Sougnez C, Onofrio R, Carter SL, Park K, Habegger L, Ambrogio L, Fennell T, Parkin M, Saksena G, Voet D, Ramos AH, Pugh TJ, Wilkinson J, Fisher S, Winckler W, Mahan S, Ardlie K, Baldwin J, Simons JW, Kitabayashi N, MacDonald TY, Kantoff PW, Chin L, Gabriel SB, Gerstein MB, Golub TR, Meyerson M, Tewari A, Lander ES, Getz G, Rubin MA, Garraway LA. The genomic complexity of primary human prostate cancer. Nature. 2011;470:214–220. doi: 10.1038/nature09744. - DOI - PMC - PubMed